Hearts exposed to sustained hemodynamic overload undergo molecular, cellular, muscular, and chamber morphologic changes that are typically maladaptive and contribute to progressive cardiac dysfunction and ultimately heart failure. Pathophysiological stimuli that trigger such responses include hypertension, valvular disease, neurohormonal stress, and excessive chamber filling associated with a decline in pump function. These trigger alterations in multiple cellular signaling and transcription pathways that induce muscle cell growth, worsened function of the heart muscle, hypertrophic remodeling and cardiac dilation.
Enlargement of the heart is a chronic and progressive condition that ultimately results in heart failure. Heart failure affects over 5 million Americans, with more than 500,000 new diagnoses annually in the United States alone. Heart failure remains the leading cause of death in the United States. Improved methods for the treatment of cardiovascular conditions, such as pulmonary hypertension and cardiac hypertrophy, are urgently required.